The Impact of Branched-Chain Amino Acid Metabolism on Limb Dysfunction in PAD

The Impact of Branched-Chain Amino Acid Metabolism on Limb Dysfunction in PAD (MicroPAD)

Test the theory that abnormalities in the large blood vessels that deliver blood to your leg and the very small blood vessels in your leg's muscles (invisible to the eye) work together to worsen your leg function and walking.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Behavioral: Vascular Assessment; Behavioral: Supervised Exercise

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion/exclusion criteria for Healthy Subjects

Inclusion criteria

• Male or female, age ≥ 50 years old
• Non-smoker

Exclusion criteria

• Presence of peripheral artery disease
• History of a heart attack or stroke
• Diabetes
• Active cancer
• Severe renal disease (CrCl < 60)
• Severe liver disease
• Active rheumatological diseases

Inclusion/exclusion criteria for PAD Subjects

Inclusion criteria

• Male or female, age 50 years or older
• Atherosclerotic PAD, ABI ≤0.85
• Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent
• For Aim 3, subjects will have Rutherford stage 4 or 5 disease
• For Aim 3, subjects will be undergoing revascularization as standard of care

Exclusion criteria

• Presence of a femoral, popliteal or tibial aneurysm of the index limb
• Life expectancy less than 2 years
• A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure
• Renal dysfunction defined as MDRD eGFR ≤ 20ml/min/173 m2 at the time of screening
• Currently on dialysis or history of a renal transplant
• Cirrhosis or active hepatitis
• A documented hypercoagulable state
• Myocardial infarction within 6 months
• Stroke within 6 months
• Nonatherosclerotic occlusive disease of the lower extremity
• Any prior infrainguinal revascularization on index limb
• Current immunosuppressive medication, chemotherapy or radiation therapy
• Inability to have an MRI
• Exercise limitation aside from that due to PAD (i.e. COPD, degenerative joint disease, etc.)
• Women who are pregnant
• Women who are nursing
• Primary indications for systemic oral anticoagulation for active arterial or venous thromboembolic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy Subjects	Behavioral: Vascular Assessment; Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age. Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy. Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.
Experimental: Peripheral Artery Disease (PAD) with Supervised Exercise; Subjects will be referred for supervised exercise therapy. Subjects will have 3 visits per week for 12 weeks. Each visit will include a minimum of 30 to 40 minutes of exercise to improve ambulation with a certified trainer.	Behavioral: Vascular Assessment; Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age. Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy. Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.; Behavioral: Supervised Exercise; Subjects will have 3 visits per week for 12 weeks.
Active Comparator: PAD Subjects Who Undergo Revascularization of the Leg; This group of subjects are receiving leg revascularization as part of standard of care.	Behavioral: Vascular Assessment; Screen: Subjects will undergo a H&P, ankle brachial index, ECG, CBC, CMP, lipid panel, HgA1C, and urinalysis. A urine pregnancy test will be performed on women of childbearing age. Testing Visit 1: MRI, IV in common femoral vein with phlebotomy (60 cc total) before and after sphygmomanometric cuff occlusion of lower limb, 6-minute walk test, 4-meter walk speed test, walking impairment questionnaire, and muscle biopsy. Supervised exercise and leg revascularization patients will return in 12 weeks and have the same study procedures as testing visit 1, plus an ankle brachial index, repeated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C3/C5acylcarnitine levels in healthy control subjects.	baseline
C3/C5acylcarnitine levels in PAD exercise group after 12 weeks	Change from baseline to 12 weeks
C3/C5 acylcarnitine levels in PAD surgical bypass group	Change from baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Joshua Beckman, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2018
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): August 22, 2023

Study Registration Dates

• First Submitted: March 30, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 180441; 18SFRN33900069 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No